Exposures that interfere with maternal, fetal or placental sex steroid metabolism may be associated with increased hypospadias risk. This proposal's goal is to use recently collected observational data to examine the association of hypospadias risk with exposures related to sex steroid metabolism. This goal will be accomplished by addressing the following specific aims: 1) To determine whether maternal intake of nutrients and food groups that affect maternal sex steroid metabolism are associated with risk of hypospadias among offspring and 2) Determine whether maternal use of corticosteroid medications is associated with risk of hypospadias among offspring. The proposed research represents the first large-scale study to explore these exposures and hypospadias risk. To accomplish the Aims, we will analyze data from a rigorously designed, multi-state, population-based case-control study, the National Birth Defects Prevention Study. The proposed research will fill an important data gap by launching forward current knowledge regarding the highly discussed but minimally studied association of endocrine-related exposures with hypospadias risk. A critical strength of this proposal is that it will utilize high quality clinical data that were collected using rigorous case ascertainment and classification criteria and detailed data on exposures and covariates. In addition to being scientifically important, the proposal is highly cost-effective, as it capitalizes on the use of existing data. The goal of this research program is to contribute to the prediction and prevention of hypospadias. The medical costs of this structural defect are huge as are the emotional costs to the affected children and their families. Little is known about the causes of hypospadias. [unreadable] [unreadable] [unreadable]